Urinary excretion of IGF-I and growth hormone in children with IDDM.

OBJECTIVE: To compare the urinary output of insulinlike growth factor I (IGF-I) and growth hormone (GH) in prepubertal and pubertal children with insulin-dependent diabetes mellitus (IDDM) versus nondiabetic subjects and to analyze the relationship between the urinary excretion of these peptides and degree of metabolic control. RESEARCH DESIGN AND METHODS: Group 1 included 30 IDDM patients who had had diabetes for 4.9 +/- 0.7 yr and had normal renal function (mean age 11.6 +/- 0.9 yr); group 2 consisted of 31 control subjects (mean age 9.2 +/- 0.6 yr). Sensitive radioimmunoassays were used to measure IGF-I and GH in urine aliquots from 12-h timed overnight collections that had been dialyzed, concentrated 50-fold, and lyophilized. RESULTS: Significantly lower IGF-I and GH outputs per kilogram body weight per 12 h were observed in IDDM subjects compared with control subjects. When data were expressed per kilogram of body weight, no difference was observed between the urinary output of IGF-I and GH between prepubertal and pubertal subjects within group 1 or group 2. The prepubertal children had significantly lower HbA1 than the pubertal population; however, no correlation was found between urinary output of IGF-I or GH and HbA1. A positive correlation was observed between urinary IGF-I and GH (r = 0.85, P less than .001). CONCLUSIONS: Patients with long-standing IDDM excrete significantly lower urinary levels of IGF-I and GH compared with normal subjects. Serial measurements of these peptides from onset of IDDM are needed to define whether the changes observed are present at diagnosis or are secondary to duration of disease.

Quantitation of urinary somatomedin-C in children with normal and abnormal growth.

The renal excretion of radioimmunoassayable somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) was measured in 12-h overnight urine samples obtained from 88 subjects, aged 3-19 yr. The participants included 34 healthy children (group 1), 29 children with idiopathic growth failure and normal GH stimulation tests (group 2), and 25 GH-deficient subjects (group 3). The mean (+/- SEM) urinary Sm-C/IGF-I excretion in group 1 (28.4 +/- 2.1 mU/kg) was significantly greater than that in group 2 (8.1 +/- 1.6 mU/kg) or group 3 (8.6 +/- 1.3 mU/kg). Twenty-two of the 29 subjects in group 2 had urinary Sm-C/IGF-I values less than 8 mU/kg. After the administration of biosynthetic GH to 12 GH-deficient subjects, urinary Sm-C/IGF-I excretion rose from 10.3 +/- 2.3 to 21.4 +/- 4.2 mU/kg within 12 h (P less than 0.05), indicating that renal excretion of Sm-C/IGF-I is GH dependent. One woman with acromegaly had markedly elevated urinary Sm-C/IGF-I excretion (420 mU/kg). The authenticity of urinary Sm-C/IGF-I was confirmed by high pressure liquid chromatography (HPLC). Assay of serial dilutions of urinary Sm-C/IGF-I demonstrated a direct proportionality between concentration and dilution. Although it is not possible to identify whether urinary Sm-C/IGF-I reflects local or generalized synthesis of the peptide, we hypothesize that quantitation of Sm-C/IGF-I in timed urine collections will yield additional information about GH production and action in children with normal and abnormal growth.

Quantitation of urinary somatomedin-C and growth hormone in preterm and fullterm infants and normal children.

Urinary GH and somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) excretion were measured in 12-h urine collections obtained from 43 infants (27 stable preterm infants and 16 healthy fullterm infants) and 31 normal children, aged 3-17 yr. Urinary Sm-C/IGF-I was excreted as the free hormone, since no binding of radiolabeled Sm-C/IGF-I to any urine protein with a mol wt similar to those described for plasma Sm-C/IGF-I-binding proteins was found. The preterm infants excreted significantly more urinary GH [13.5 +/- 2.1 (+/- SE) ng/kg.12 h] than either the fullterm infants (5.3 +/- 1.6 ng/kg.12h) or the children (0.27 +/- 0.02 ng/kg.12 h; P less than 0.01). The mean urinary Sm-C/IGF-I excretion in the preterm infants (98.9 +/- 7.5 mU/kg.12 h) was comparable to that in fullterm infants (87.6 +/- 9.7 mU/kg.12 h); both groups excreted significantly more urinary Sm-C/IGF-I than children (28.4 +/- 2.1 mU/kg.12 h; P less than 0.01). The group differences were similar when the results were expressed in terms of creatinine excretion. Urinary GH excretion correlated positively with urinary Sm-C/IGF-I excretion (r = 0.68). The higher output of these peptides in rapidly growing infants and their positive correlation in urine provide additional support for the Sm hypothesis.

Diagnostic value of the growth hormone-releasing factor stimulation test.

Growth hormone (GH) responses to growth hormone-releasing factor (GRF) were evaluated in 55 children with growth failure. The study groups consisted of group 1, severe GH deficiency; group 2, partial GH deficiency; group 3, patients with prior cranial radiation for nonpituitary brain tumors; and group 4, children with idiopathic growth failure. Children in group 1 were unresponsive to GRF (mean GH peak +/- SEM, 1.6 +/- 0.5 ng/ml). Higher GH responses to GRF were observed in both groups 2 (17.2 +/- 4.1 ng/ml) and 3 (10.4 +/- 2.8 ng/ml). The highest GH responses to GRF were observed in group 4 (35.9 +/- 4.3 ng/ml). ANOVA revealed a significant difference between groups (F = 12.9; df = 3; p less than 0.01), and further analysis by the Scheffe and Student-Newman-Keuls tests revealed that group 4 was significantly higher than groups 1, 2, or 3 (p less than 0.05). These data suggest that GRF unresponsiveness is a reliable predictor of severe GH deficiency. In patients with partial GH deficiency or idiopathic growth failure, the GRF gives semiquantitative information about somatotrope responsivity to exogenous stimulation.

Triad of hypopituitarism, granulomatous hypophysitis, and ruptured Rathke's cleft cyst.

A 19-year-old girl with pituitary insufficiency and a large sella turcica was found to have granulomatous hypophysitis in association with a Rathke's cleft cyst. We think that the inflammatory process represents a foreign body reaction to leakage of cyst contents, with destruction of pituitary tissue.

Soluble interleukin 2 receptor levels in children with type I insulin-dependent diabetes mellitus.

Soluble interleukin 2 receptor (sIL-2R) levels reflect mononuclear cell activation and are elevated in a variety of autoimmune, neoplastic and infectious conditions. Several investigators have studied sIL-2R levels in patients with Type I diabetes mellitus (IDDM), but results have been conflicting. Our primary objective in this study was to compare sIL-2R levels of children and adolescents with newly diagnosed IDDM with those of age-matched controls. In addition, sIL-2R levels in a cohort of patients were followed longitudinally for 1 to 2 years after diagnosis. Serum sIL-2R levels of 38 IDDM children and adolescents (age < 20 years) were compared with levels of 39 nondiabetic, age-matched controls. Mean sIL-2R levels declined with age (P < 0.000005), and there was no significant difference in the regression line relating age and sIL-2R levels between patients and controls. The sIL-2R levels remained fairly consistent over 1-2 years of follow up. The presence of islet cell antibodies (ICA) had no apparent effect on sIL-2R levels in children with diabetes. The sIL-2R levels were similar in magnitude among first degree relatives of patients with IDDM compared to the range of unrelated subjects. It is our conclusion that sIL-2R levels are highest during infancy and decline throughout childhood. The sIL-2R levels do not appear to be clinically useful as a reflection of immune activation in patients with IDDM. Finally, there may be a genetic influence which partially regulates production of sIL-2R.

Urinary growth hormone and insulin-like growth factor I. Effects of growth-hormone injection schedule.

Urinary growth hormone (GH) and insulin-like growth factor I (IGF-I) excretion profiles were compared in children receiving biosynthetic GH. Group 1 included 18 healthy controls. Group 2 included nine children given biosynthetic GH three times a week. Group 3 included 14 children given daily GH injections. Overnight urine samples were collected for three consecutive nights in all groups. No significant day-to-day variation in urinary GH output was observed in group 1. In group 2, urinary GH output was significantly higher on day one following injection than on days two and three. Urine GH outputs in group 2 were significantly lower on days two and three than the values observed on all days in group 3. Throughout the three-day study, subjects in group 3 excreted similar amounts of GH significantly higher than those of controls. Urinary IGF-I output (nmol/kg) was similar on all three study days in groups 1 and 3. Group 2 had significantly lower urinary IGF-I output on day three compared with day one. Urinary IGF-I output on day three was also significantly lower in group 2 than in group 3. We conclude that urinary GH and IGF-I outputs are influenced by the frequency of GH administration.

Microalbuminuria in an adolescent cohort with insulin-dependent diabetes mellitus.

To document the incidence of microalbuminuria in children and adolescents with longstanding insulin-dependent diabetes mellitus (IDDM) and to compare the clinical characteristics and determinant risk factors of those with and without microalbuminuria, 135 adolescent patients with IDDM for 5 years or longer were evaluated. The study population was divided on the basis of microalbumin excretion into normal (< 20 micrograms/min), incipient (20-200 micrograms/min), and overt (> 200 micrograms/min) nephropathy groups. There were 106 patients in the normal group, 24 patients in the incipient group, and five in the overt nephropathy group. Glycosylated hemoglobin, cholesterol concentration, and glomerular filtration rate (GFR) were analyzed. The incidence of incipient and overt nephropathy was 17.8% and 3.7%, respectively. Mean cholesterol concentration in the incipient and overt nephropathy groups (208 +/- 39 mg/dL [5.4 +/- 1.0 mmol/L]) and 227 +/- 49 mg/dL [5.9 +/- 1.3 mmol/L], respectively) was significantly higher than the normal group (186 +/- 37 mg/dL [4.8 +/- 0.9 mmol/L] P < 0.05). Similarly, systolic and diastolic blood pressures were significantly higher in the incipient and overt nephropathy groups compared to the normal group. This study confirms the high incidence of incipient and overt nephropathy in adolescents with IDDM early in the course of the disease.

Incidence of celiac disease identified by the presence of serum endomysial antibodies in children with chronic diarrhea, short stature, or insulin-dependent diabetes mellitus.

We determined the incidence of celiac disease in the western New York area to be 1.29 per 10,000 live births. Celiac disease occurred in 29 children with gastrointestinal symptoms. Two children (1.7%) of 117 with short stature and 10 (4.0%) of 211 with diabetes mellitus had serum anti-endomysial antibodies. We conclude that the incidence of childhood celiac disease in our area is much less than that reported in Europe.

[Incidental carcinoma of the prostate]. / Il carcinoma incidentale della prostata.

The purpose of this study has been to establish the possible presence of incidental carcinoma among men with benign prostatic hyperplasia. During the period 1983-1987, 954 patients with benign prostatic hyperplasia, have been undergone transvesical prostatectomy. Prostatic tissue has been studied with sagittal sections. Sections on the surgical specimens were taking every 0.5 Cm. In this way we have obtained from 6 to 15 sections in every prostate gland for microscopic examination. The incidence of incidental carcinoma of the prostate was found to be 5.45 per cent and it represent 24.88 per cent of all prostatic adenocarcinomas.

Urinary insulin-like growth factor-II excretion in healthy infants and children with normal and abnormal growth.

The output of urinary IGF-II was measured by RIA in 12-h overnight urine samples obtained from 22 preterm and 15 full-term infants, 40 normal children, 18 children with growth hormone (GH) deficiency, and 25 patients with idiopathic short stature. GH deficiency was defined as a peak to GH provocative tests < or = 9.9 micrograms/L during two provocative tests. The authenticity of urinary IGF-II was confirmed by size exclusion chromatography. Statistical analysis was performed by one-way analysis of variance using the Student Neuman-Keuls test to detect intergroup differences at the level of p < 0.05. The preterm and full-term infants excreted significantly higher amounts of urinary IGF-II (18.4 +/- 1.7 and 5.7 +/- 1.0 pmol/kg, respectively) compared with normal children (2.4 +/- 0.25 pmol/kg; p < 0.001). The output of urinary IGF-II in preterm infants was greater than that observed in full-term infants (F = 84.7, p < 0.001). The control children excreted significantly more IGF-II (2.4 +/- 0.2 pmol/kg) than children with GH deficiency (0.9 +/- 0.1 pmol/kg) or idiopathic short stature (1.0 +/- 0.1 pmol/kg; F = 13.5; p < 0.001). Analysis of urinary IGF-II excretion based on creatinine output yielded similar results. Data on urinary IGF-I and GH previously published were correlated and compared with the excretion pattern of urinary IGF-II.(ABSTRACT TRUNCATED AT 250 WORDS)

Prescription practices of diagnostic imaging in dementia: a survey of 47 Alzheimer's Centres in Northern Italy.

BACKGROUND: To date, there are no data at the national or European level on the prescription practices of imaging (CT, MR, and SPET) in the diagnosis of cognitively impaired elderly patients. METHODS: We addressed prescription practices of diagnostic imaging in 47 Alzheimer's Centres in Northern Italy, with an ad-hoc questionnaire. RESULTS: The use of imaging in new cases was relatively intensive: 62% of the Alzheimer's Centres prescribed CT to more than 95% of cases, 24% prescribed MR to more than 33% of cases, and 33% prescribed SPET to more than 5% of cases. A minority of Alzheimer's Centres (n = 3, 6%) prescribed imaging to less than 100% of new cases. The association between onsite scanner availability and frequency of prescription increased from CT (Odds ratio (OR) = 1.8) through MR (OR = 2.4) to SPET (OR = 4.6), although only the latter was significant (95% confidence interval (CI) 1.2-17.7, p = 0.003). Patient-related factors (age, severity of cognitive impairment, and clinical suspicion of cerebrovascular disease) influenced prescription of structural imaging in 30-53% of Alzheimer's Centres and organizational factors (onsite scanner availability, and waiting list) in a similar proportion (32 and 43% respectively). CONCLUSIONS: Organizational factors play a relevant role in the prescription of imaging exams in patients with cognitive impairment and, at least for CT, the perceived diagnostic added value is rather low, suggesting a high degree of uncertainty in the clinical use of imaging techniques.

Comparison of urinary growth hormone and IGF-I excretion in small- and appropriate-for-gestational-age infants and healthy children.

The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12-h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean +/- SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (micrograms/kg): PT-SGA 13.7 +/- 3.1 versus PT-AGA 14.0 +/- 2.2, FT-SGA 7.8 +/- 2.4 versus FT-AGA 6.6 +/- 1.8; IGF-I (nmol/kg): PT-SGA 0.52 +/- 0.09 versus PT-AGA 0.53 +/- 0.04, FT-SGA 0.31 +/- 0.05 versus FT-AGA 0.35 +/- 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p less than 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and beta-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation of urinary growth hormone in children with normal and abnormal growth.

Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean +/- SEM per kg body weight) in group 1 (0.27 +/- 0.02 ng/kg) was significantly greater than group 2 (0.08 +/- 0.02 ng/kg) or group 3 (0.17 +/- 0.02 ng/kg, p less than 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 +/- 0.07 versus 0.12 +/- 0.02 ng/kg, p less than 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess.

Transplacental transmission of antibodies to tubular basement membrane in guinea-pigs with autoimmune tubulointerstitial nephritis.

The offspring of female guinea-pigs with tubulo-interstitial nephritis were studied for possible passive transfer of disease. Whereas no immune deposits were seen on or before day 30 of gestation, IgG was detected in the tubular basement membrane (TBM) of fetuses at and after day 44. Serum of offspring contained antibodies to TBM, albeit in much lower titres than found in circulation of the mother guinea-pigs. No histopathological changes were seen in fetal kidneys. Thus, autoantibodies induced by heteroimmunization of pregnant guinea-pigs may be transmitted to offspring in the last third of the gestation period and can bind to fetal TBM. However, this transfer of antibodies does not cause disease.

Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone.

Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 +/- 0.3 versus 3.4 +/- 0.2 micrograms/L); group 2 had significantly lower GH concentrations (1.6 +/- 0.2 micrograms/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 +/- 2.6 nmol/L, p less than 0.001) than in groups 2 and 3 (2.6 +/- 0.5 and 5.5 +/- 0.7 nmol/L, respectively). Urinary GH (mean +/- SEM) standardized for body weight (micrograms/kg) in group 1 (0.31 +/- 0.02) was significantly greater than in group 2 (0.14 +/- 0.01) and group 3 (0.20 +/- 0.01). However, when expressed as microgram/mol creatinine, the output of GH was similar in group 1 (4.0 +/- 0.3) and group 3 (3.4 +/- 0.3); both groups had significantly greater output compared to group 2 (1.3 +/- 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 +/- 0.02) was significantly greater than in group 2 (0.12 +/- 0.01) or group 3 (0.07 +/- 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p less than 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.

Calcium antagonists and hormone release. V. Effects of a calcium-antagonist (verapamil) on pituitary hormone release in hypersecretory states.

Twenty-five patients with various syndromes of pituitary hyperfunction, of tumoral and nontumoral origin, were infused with verapamil (VE), a Ca2+-channel blocker (5 mg/h X 3 h) to assess the calcium dependence of the augmented hormone secretion. In 5 hypogonadal women with elevated gonadotropin secretion, VE produced a marked inhibition of LH (54.6%) and FSH (49.4%) release, comparable to that observed in normal subjects who were infused with VE. In 5 patients with latent or mild hypothyroidism, TSH levels decreased during the VE infusion, and the magnitude of the decrease was directly correlated with the basal levels (r = 0.986, p less than 0.01). In patients harboring a pituitary tumor, differential effects of VE infusion were observed: it induced an inhibition (28.5%) of ACTH secretion in patients with Cushing's disease; in acromegalic patients, no alterations in HGH levels were noted; on the contrary, in prolactinoma patients, a clear PRL increment (47.2%) was present. These experiments confirm that the need for extracellular Ca2+ varies from hormone to hormone and that VE infusion can modify the secretion of pituitary hormone in a hypersecretory state, as well as those hormones which are unaffected by VE infusion in basal condition.